Lipid Metabolism and Cardiac Test Markers: Importance of Standardization

Transcription

1 Lipid Metabolism and Cardiac Test Markers: Importance of Standardization Barbara M. Goldsmith, Ph.D., FACB Vice President, Marketing, Membership and Education Clinical and Laboratory Standards Institute (CLSI)

2 Outline of Presentation CLSI Background Information Standards and Guidelines Lipid Standardization and Traceability Cardiac Markers and Risk Assessment Summary 2

3 Our Common Goal: Quality Healthcare

4 CLSI Background Established in 1968 Nonprofit organization based in the United States American National Standards Institute (ANSI) accredited standards-development organization Volunteer driven through our governance structure and technical operations An organization of organizations More than 200 standards and guidelines

5 CLSI Name Name change in 2005 to reflect global constituencies

6 CLSI s Vision To be the leader in clinical and laboratory standards to improve the quality of medical care.

7 CLSI s Mission To develop best practices in clinical and laboratory testing and promote their use throughout the world, using a consensus-driven process that balances the viewpoints of industry, government, and the health care professions.

8 CLSI Today $7M annual budget 45 employees 2,000 member organizations nearly 2,000 active volunteers (>600 Non-North American memberships, >70 countries) consensus standards and guidelines >75,000 documents each year distributed

9 CLSI Consensus Process Government Balance Industry Professions 9

10 CLSI consensus process Meetings are open to everyone Meeting materials are fully available Balanced interests Conflicts of interest are fully disclosed Appeals process All comments addressed

11 CLSI products Standards Guidelines Collections Videos Toolkits Reports ISO documents

12 New method evaluation software Developed in conjunction with Analyse-it Benefits Software Only software to faithfully implement the eight most popular CLSI method evaluation guidelines Evaluates and verifies performance characteristics of laboratory methods Provides clear step-by-step advice on performing a study Delivers tools for accreditation preparedness Easy-to-use workflow Provides timely, accurate statistical results Professional reports, customizable graphs and charts Large hospital laboratories Small hospital laboratories Physician office laboratories Reference laboratories In vitro diagnostic customer support departments

13 Use of CLSI Documents Regulatory Compliance - Compliance with recognized CLSI consensus documents to facilitate regulatory review of IVD devices. Professional Practice - Implementation of CLSI best practices for accreditation preparedness Education in Clinical Laboratory Sciences Translations include: - Japanese -Spanish - Korean (In progress) -Turkish - Portuguese -Chinese (In progress) - Russian - German

14 Adoption of Documents into Accreditation Process Example of Crosswalk 14

15 CLSI Members & Volunteers Diverse representation from three constituencies Industry Government Professions IVD Manufacturers Public Health Agencies Hospitals and Laboratories LIS Vendors Regulatory Bodies Healthcare Delivery Systems Startup Companies Accrediting Organizations Educational Institutions Suppliers Others Professional Societies Trade Organizations 15

16 CLSI Area Committees Automation and Informatics Clinical Chemistry and Toxicology Evaluation Protocols Hematology Immunology and Ligand Assay Microbiology Molecular Methods Point-of-Care Testing Quality Systems and Laboratory Practices

17 Global Health Partnerships Grant funding from U.S. government 10 staff members More than 60 volunteers qualified as trainers 17

18 Global Health Partnerships CLSI Lab Strengthening Program Services: Assessment/Gap Analysis Training and Education Mentoring Laboratory Self-assessment Continuous Quality Improvement

19 Global Health Partnerships Current programs planned or underway in - Côte d Ivoire Mali - Tanzania Azerbaijan - Ethiopia Georgia - Namibia Uzbekistan - Vietnam Kazakhstan - Nigeria Ghana

20 Preparing laboratories for WHO-Afro accreditation Cote d'ivoire Nigeria Senegal Ethiopia Rwanda Botswana

21 CLSI s Key Global Activities International Organization for Standardization (ISO) CLSI is Secretariat for ISO Technical Committee 212 Clinical Laboratory Testing and in vitro Diagnostic Test Systems and its working groups: WG 1: Quality and competence in the medical laboratory. WG 2: Reference Systems WG 3: In vitro diagnostic products WG 4: Antimicrobial susceptibility testing CLSI is administrator of the ANSI-Accredited US Technical Advisory Group (TAG) to ISO/TC 212.

22 Relationship of CLSI and ISO Standards broad, standard requirements detailed help and practical guidance Complimentary, not conflicting, roles

23 Standards and Guidelines 23

24 Standards & the Lab Most medical lab errors are caused by systems and process issues, not people. They are the areas where standards can help the most.

25 Why do Standards Matter? Raise levels of quality, safety, reliability, efficiency, and interchangeability Lower trade barriers Act as a base for legislation (or avoid the need for legislation) Aid in technology transfer Provide easy access to best-in-class practices Deliver improved outcomes at an economical cost 25

26 Standards Development Consensus Process A consensus standard or guideline is a document developed to promote uniform products, materials, methods, or practices. Levels of the consensus process: Proposed Level Approved Level 26

27 Standard or Guideline? A standard must be followed exactly as written. - Written using verbs such as will, must, and shall A guideline may be modified by the user. - Written using verbs such as should, could, may, or might 27

28 Standardization and Traceability 28

29 Reasons for testing To identify individuals at increased risk of disease and/or monitor disease management To develop epidemiologic data from which to establish public health strategies for disease management G. Myers, CDC, with permission

30 Requirements to meet testing goals Precise and accurate assays Results must be comparable, independent of where and when test performed and assay used Specific measurement standards of higher order Reference measurement procedure(s) (RMP) Reference laboratories that provide RMPs Reference material(s) Process or program to establish and maintain traceability to established standards G. Myers, CDC, with Permission

31 Standardization of Laboratory Results In the context of laboratory medicine we really mean Metrological Traceability G. Myers, CDC, with permission

32 Traceability: ISO Definition Traceability - property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties. G. Myers, CDC, with permission

33 Traceability in Laboratory Medicine Tools Needed for Traceability Reference measurement procedure(s) Gold Standard Reference MP Laboratories Reference materials (commutable) G. Myers, CDC, with permission

34 Metrological Traceability Traceability in Laboratory Medicine RMP Patient Sample Result process that ensures patient sample results by a routine measurement procedure are equivalent to RMP results Reference Materials (commutable) Routine MP Patient Sample Result G. Myers, CDC, with permission

35 Standardization vs. Proficiency Testing Standardization is NOT the same as proficiency testing (PT) Most PT programs in the US are NOT accuracybased programs PT programs use peer-group grading where laboratories are evaluated using the group mean for a particular instrument/method Standardization programs must be accuracy-based and provide an analytical anchor for traceability purposes G. Myers, CDC, with permission

36 To establish traceability and be standardized, a laboratory must be: Precise and Accurate Accurate, not precise Neither accurate nor precise RMP Precise, not accurate Precise and accurate G. Myers, CDC, with permission

37 When and Why Is Traceability Most Important? To insure the reliability and comparability of research findings across studies When patients are seen in a variety of health care settings, each using different clinical labs When patient s clinical test results are being compared to guidelines from the medical literature and/or large national or international research studies (e.g., estimated GFR for CKD, HbA1c for diabetes, cholesterol for CVD, etc.). G. Myers, CDC, with permission

38 Three Separate Measurement Components that Require Traceability to Reference Standards Research Laboratories that support investigational studies Manufacturers that develop and provide routine clinical assays Clinical laboratories that provide test results for assessing risk and monitoring therapy G. Myers, CDC, with permission

39 Calibration Traceability Scheme Primary Calibrator Reference procedure (GC-IDMS or LC-IDMS) Reference Laboratories Calibration Patient Sample Correlation Calibration SRM Proficiency Testing Commutable Samples Manufacturer Clinical Lab. G. Meyers

40 Calibration Hierarchy Traceability Chain for Cholesterol Measurement NIST IDMS SRM 1951b 1º reference material SRM 911 (pure cholesterol standard) CDC 2º reference materials Fresh sample comparison Mfr working calibrator CDC AK CRMLN AK Manufacturer Metrological Traceability Clinical Laboratory QC and GLP Patient G. Myers, CDC, with permission

41 Reference Measurement Procedure, HDL & LDL Beta-quantification 1. Ultracentrifuge serum Rem. IDL Lp(a) Apo E Chylo VLDL LDL HDL 2. Hep/Mn ++ precipitate HDL LDL 3. Abell-Kendall Chol. (LDL + HDL) HDL = LDL G. Myers, CDC, with permission

42 Lipoproteins include a range of particles UC density cut Hep-Mn ppt Hep-Mn soluble Used with permission

43 Beta-quantification limitations A range of lipoprotein particles are included in HDL, LDL and VLDL fractions Consequently, the measurand is poorly defined Lipoproteins may be distributed differently in diseased vs. normal serum A particular lipoprotein may be present in unusually high proportion A lipoprotein that is normally a minor component may be present in relatively high concentration G. Myers, CDC, with permission

44 NCEP performance criteria Total Error Bias* CV* TC 9% 3% 3% HDL-C 13% 5% 4% a LDL-C 12% 4% 4% TG 15% 5% 5% *Suggested limits to meet TE requirement a CV 4% at 42 mg/dl; SD 1.7 at 42 mg/dl Clinical Chemistry 1988;34: (TC), and 1995;41: (HDL,LDL, TG) NCEP = National Cholesterol Education Project

45 SIGNAL Routine Method Trueness (accuracy) Traceability Manufacturer comparison with a CDC Network Reference Lab Patient Specimens Traceability to the reference system is through the manufacturer s method specific calibrators Reference Method Routine Method Calibration Calibrator value Reportable patients results are traceable to Cannot mix calibrators and reagents from different manufacturers G. Myers, CDC, with permission

46 Lipids: method evaluation Precision CLSI EP5 Bias vs. RMP using patient specimens CLSI EP9 Interferences G. Myers, CDC, with permission

47 Lipids: method evaluation Interferences: Metabolites, drugs (e.g. Hb, bilirubin, ascorbate) that cause a measurement interference CLSI EP7 Distinguish between a measurement interference and a physiologic effect E.g. bilirubin can cause spectrophotometric effect, react with H 2 O 2, and correlates with liver disease that may produce an abnormal lipoprotein (e.g. LpX) G. Myers, CDC, with permission

48 Lipids: method evaluation Interferences: Method non-specificity is important Influence on physicochemical separation of lipoprotein molecular forms To normal lipoproteins in abnormal concentrations To abnormal lipoproteins To other proteins CLSI EP21 total error G. Myers, CDC, with permission

49 Homogeneous HDL-C: approach 1 Step 1: prevent reaction of non-hdl-c Y + - Chylo VLDL LDL + - Y Y Y Step 2: convert HDL-C to a measurable substance Y Y HDL Chol esterase Chol oxidase Dye Peroxidase COLOR G. Myers, CDC, with permission

50 Homogeneous HDL-C: approach 2 1. Protect HDL-C from reaction and convert non-hdl- C to non-measurable substances HDL - Chylo VLDL LDL Chol esterase Chol oxidase Catalase NO COLOR 2. Un-protect HDL-C and convert to a measurable substance + - HDL + - HDL Dye Peroxidase COLOR G. Myers, CDC, with permission

51 Homogeneous LDL-C: analogous to HDL-C 1. Protect + non-ldl Chylo VLDL HDL Convert LDL-C Chol esterase Chol oxidase Dye Peroxidase LDL COLOR 1. Protect LDL and convert non-ldl-c LDL Chol esterase Chol oxidase Catalase Chylo VLDL HDL NO COLOR 2. Unprotect and convert LDL-C Dye LDL LDL Peroxidase COLOR G. Meyers, CDC, with permission

52 Homogeneous measurement challenges Measure the same lipoprotein fractions that are measured by beta-quant Not measure anything else Do it for a wide range of clinical conditions with abnormal lipoproteins and other proteins Do it with acceptable total error for individual samples (not just trueness and imprecision) and cost G. Myers, CDC, with permission

53 Why is standardization important clinically?

54 Comparison of HDL and LDL Cholesterol Methods to Reference Measurement Procedures Background: Current guidelines on use of LDL-C and HDL-C for cardiovascular risk assessment based on early epidemiologic studies that established link between lipoproteins and cardiovascular disease Based on older methods that depended on physical separation of different lipoprotein classes and not direct methods Direct measurements prompted by NCEP panel that stated LDL-C should be measured directly Miller WG et al Clin Chem 56: (2010) 54

55 Comparison of HDL and LDL Cholesterol Methods to Reference Measurement Procedures Methods from 7 manufacturers and 1 distributer for direct measurement of HDL-C and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples 6 of 8 HDL-C and 5 of 8 LDL-C direct methods met NCEP total error goals for non-diseased individuals Patients included individuals with and without disease and patients with various types of lipoprotein disorders (unlike previous studies) All methods failed to meet NCEP goals for diseased individuals due to lack of specificity toward abnormal lipoproteins Miller WG et al Clin Chem 56: (2010) 55

56 Comparison of HDL and LDL Cholesterol Methods to Reference Measurement Procedures Authors Conclusions: NCEP accuracy goals based on laboratory testing when guidelines were developed (e.g. precipitation-based methods for HDL-C, Friedewald equations for LDL-C) and clinical need to classify CHD risk and monitor lipid treatment (drugs) Composition of lipoproteins in various dyslipidemias affect direct methods in specifically measuring cholesterol content of one lipoprotein class in presence of other lipoproteins; challenging for manufacturers of direct methods Miller WG et al Clin Chem 56: (

57 Comparison of HDL and LDL Cholesterol Methods to Reference Measurement Procedures Authors Conclusions (Con t) Cannot rule out interferences (drugs, comorbidities, triglycerides, nutrition, nonfasting specimens) Differences between direct methods and RMPs could affect diagnosis and clinical management of patients 30-45% test results outside of NCEP total error goals for some methods; could reduce overall effectiveness of screening for CV risk assessment Miller WG et al Clin Chem 56: (

58 Cardiac Markers and Guidelines

59 National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines (LMPG)

60 Published NACB LMPGs Therapeutic Drug Monitoring 1999 Cardiac Markers 1999 Hepatic Injury 2000 Diabetes Mellitus 2002 Thyroid Disease (2nd edition) 2002 Tumor Markers in the Clinic 2003 Emergency Toxicology 2005 Maternal-fetal Risk Assessment 2006 Biomarkers of ACS 2007 * Point of Care Testing 2007 Tumor Marker Quality Requirements 2009 Expanded Newborn Screening 2009 Emerging Biomarkers for CV Risk Factors 2009 * Major Tumor Markers 2009 Pharmacogenetics 2010 Liver Tumor Markers 2010

61 NACB LMPG: Biomarkers of Acute Coronary Syndrome (ACS) (Published 2007) 61

62 Steps to consider in evaluating Biomarkers Is concentration different in persons affected by disease in comparison to those not affected Is there a body of evidence from case-control and prospective studies that have evaluated the test Does measurement improve ability to assess risk above and beyond current approaches Are there reliable analytical methods available for measurement NACB LMPG, ACS,

63 Risk Stratification of Acute Coronary Syndromes (ACS) Tools: History and physical Standard ECG and non-standard ECG leads Cardiac biomarkers (Troponin I or T, CK-MB, Myoglobin, others) Predictive indices/schemes (better as research tools than for real-time decision-making) Non-invasive imaging studies (echo, stress test) NACB LMPG, ACS, 2007

64 NACB Guideline Recommendations (selected recommendations for ACS) Biomarkers of myocardial necrosis should be measured in all patients who present with symptoms consistent with ACS Cardiac troponin is the preferred marker for the diagnosis of MI. CK-MB by mass assay is an acceptable alternative when cardiac troponin is not available Blood should be obtained for testing at hospital presentation followed by serial sampling with timing of sampling based on clinical circumstances. For most patients, blood should be obtained at presentation, 6-9 hrs, and hrs if earlier sample negative Note Recommendation Classes omitted

65 NACB Recommendations (Con t) For patients who present within 6 hrs of onset of symptoms, an early marker may be considered in addition to troponin. Myoglobin is the most extensively studied marker for this purpose Total CK, AST, beta-hydroxybutyric dehydrogenase, and/or LD should NOT be used as biomarkers for the diagnosis of MI NACB LMPG, ACS, 2007

66 NACB Recommendations (Con t) A cardiac troponin is the preferred marker for risk stratification and, if available, should be measured in all patients with suspected ACS. In patients with a clinical syndrome consistent with ACS, a maximal concentration exceeding the 99 th percentile of values for a reference control group (with acceptable precision) should be considered indicative of increased risk of death and recurrent ischemic events NACB LMPG, ACS, 2007

67 Death or MI Troponin as a Marker of Increased Risk in ACS 40% 30% 30% 34% Troponin + Troponin - 22% 23% 20% 19% 19% 12% 11% 12% 10% 0% 2% Hamm (1992) FRISC (1996) 4% 4% TRIM (1999) Pettijohn (1997) 1% Hamm (1997) 0% Hamm (1997) 6% Polanczyk (1998) 6% Galvanni (1997)

68 Strengths of Troponin as biomarker: Almost 100% sensitivity for acute MI with serial draws Cardio-specific Remains elevated in circulation up to 7 days Excellent for retrospective diagnosis of acute MI Best prognostic indicator for ACS NACB LMPG, ACS, 2007

69 Limitations of Troponin Not an early marker No standardization of methods across troponin I assays from different manufacturers Sporadic elevations from minor myocardial damage may confuse interpretation NACB LMPG ACS, 2007

70 Not all Troponins are Alike Analytical recommendations (NACB Guidelines): 99 th percentile with a CV <10% Troponin I-multiple manufacturers; issue with standardization Troponin T-only one manufacturer (Roche); no issue with standardization Cutoffs NOT interchangeable NACB LMPG, ACS, 2007

71 FDA Approved Cardiac Troponin Assays

72 Myoglobin Early rising necrosis marker Rises within 1-3 hours of onset of ACS Doubles in concentration over a two hour period Specificity of >95-98% for acute MI 2 negative results 2 hours apart rules out acute MI in 97-99% patients NACB LMPG, ACS, 2007

73 Limitations of Myoglobin Can be cleared in 6 hrs Present in cardiac and skeletal muscle (non-specific) Elevated in muscle trauma and renal dysfunction NACB LMPG, ACS, 2007

74 Optimal TAT for Cardiac Biomarkers for ACS NACB Recommendations: Laboratory should perform cardiac marker testing with TAT of 1 hour, optimally 30 minutes or less. TAT defined as time from blood collection to the reporting of results Institutions that cannot consistently deliver cardiac marker TAT of 1 hour should implement POC platform Acceptable harmonization to central lab results should be < 20% NACB LMPG, ACS, 2007

75 NACB Recommendations-BNP Plasma BNP or NT-proBNP testing should be performed to confirm the diagnosis of HF in patients with suspected diagnosis, but with presenting signs and symptoms that are ambiguous with confounding disease (COPD) In diagnosis of patients with HF, routine plasma BNP or NT-proBNP with obvious clinical diagnosis is not necessary NACB LMPG, ACS, 2007

76 BNP and NT-proBNP - NACB Recommendations No primary reference materials are validated for calibration of BNP or NT-proBNP. Harmonization around the current presumed optimal diagnostic medical decision cutoff of 100 pg/ml for BNP should be validated. There is only one source of antibodies and calibrators for NT-proBNP so harmonization of NT-proBNP assays should not be a problem NACB LMPG, ACS, 2007

77 BNP and NT-proBNP NACB Recommendations Normal reference limits (95 th or 97.5 th percentile) should be independently established for both BNP and NT-proBNP based on age (by decade) and by gender. Each commercial assay should be validated separately. The effect of ethnicity needs to be evaluated as a possible independent variable NACB LMPG, ACS, 2007

78 National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines (LMPG): Emerging Biomarkers for Primary Prevention of Cardiovascular Disease and Stroke (Published 2009) 78

79 Emerging Risk Factors for Cardiovascular Disease C-Reactive Protein Serum amyloid A Soluble CD-40 ligand Fibrinogen D-dimer Factovs V,VII,VIII Lipoprotein(a) LDL and HDL subtypes Homocysteine Microalbuminuria Cystatin C Apo E genotype Remnant lipoproteins Interleukins (eg, IL-6) Vascular and cellular adhesion molecules Leukocyte count Plasminogen activator inhib 1 Tissue-plasminogen activator Small dense LDL Apoliproproteins A1 and B Oxidized LDL Lipoprot-assoc phopholipasea2 Creatinine (GFR) Infectious agenst Fibrinopeptide A Von Willebrand factor antigen NACB LMPG Emerging Biomarkers for CVD

80 Biomarkers and Cardiovascular Disease Risk NACB Guidelines Inflammation Biomarkers * Lipoprotein Subclasses and Particle Concentration Lipoprotein (a) Apolipoproteins A-I and B * Markers of Renal Function Homocysteine * Natriuretic Peptides (BNP and NT-proBNP)

81 Inflammation Biomarkers and Cardiovascular Disease Risk - hscrp High-sensivity C-Reactive Protein (hscrp) Recommendation 1: After standard global risk assessment, if the 10-year predicted risk is <5%, hscrp should not be measured Recommendation 2: If risk is intermediate (10-20%) and uncertainty remains as to the use of preventive therapies (statins or aspirin) then hscrp measurement might be useful for further stratification into a higher or lower risk category NACB LMPG, CVD, 2009

82 Inflammation Biomarkers and Cardiovascular Disease Risk (Cont) Recommendation 3 There are insufficient data that therapeutic monitoring using hscrp over time is useful to evaluate effects of treatments in primary prevention Recommendation 4 The utility of hscrp concentrations to motivate patients to improve lifestyle behaviors has not been demonstrated Recommendation 5 Evidence is inadequate to support concurrent measurement of other inflammatory markers in addition to hscrp for coronary risk assessment NACB LMPG, CVD,

83 Apolipoproteins A-I and B and Cardiovascular Disease Risk Recommendation 1 The first step to monitor efficacy of lipid lowering therapies is to measure LDL-C (and non-hdl-c) in patients with elevated triglycerides Recommendation 2 Although apob measures atherogenic lipoproteins and is a good predictor of CVD risk (equal at least to LDL-C and non-hdl- C), it is only a marginally better predictor than the current lipid profile and should not be routinely measured at this time for use in global risk assessment NACB LMPG, CVD,

84 Apolipoproteins A-I and B and Cardiovascular Disease Risk Recommendation 3 Measurement of apo-b can be used to monitor efficacy of lipid-lowering therapies as an alternative to non-hdl-c Recommendation 4 The apo B/apo A-I ratio can be used as an alternative to the usual total cholesterol/hdl-c ratio to determine lipoproteinrelated risk for CVD Recommendation 5 Manufacturers of apo-b and apo-a I assays should establish traceability to accepted standards to assure reliable and comparable results NACB LMPG, CVD,

85 Homocysteine (Hcy) and Cardiovascular Disease Risk Recommendation 1 Hcy concentrations (umol/l) derived from standardized assays categorize patients as follows: Desirable < 10 Intermediate (low to high) >10 to <15 High > 15 - <30 Very high > 30 NACB LMPG, CVD,

86 Homocysteine and Cardiovascular Disease Risk Recommendation 2 The analytical performance goal for clinical usefulness for measurement of Hcy should be <10% for bias, <5% for precision, and <18% for total error. Manufacturers of diagnostic assays for Hcy should follow approved value transfer protocols to assure that standardized assays are used for vascular risk assessment NACB LMPG, CVD,

87 NACB LMPG Point of Care Testing (Published 2007)

88 Point of Care Cardiac Markers Benefits of cardiac marker POCT: Reduced bottleneck in the ED Identification of cardiac patients more quickly Reduce inappropriate treatment pathways Allow for more rapid rule-out of a cardiac event Reduction in LOS for chest pain, CHF, and MI

89 NACB Guideline Recommendations- Evidence- Based Practice for Point of Care Testing : POC Cardiac testing The laboratory should perform cardiac marker testing (for the ED) with a TAT of 1 hour, optimally 30 minutes or less. TAT is defined as the time from blood collection to the reporting of results Comments: timeframe required to determine need for thrombolytic therapy. Rule out of MI requiring serial samples diminishes the need for a very rapid TAT on any single sample NACB LMPG, POC, 2007

90 NACB POC Cardiac Marker Recommendations (Con t) Institutions that cannot consistently deliver cardiac marker TAT of approximately 1 hour should implement POC testing devices Performance characteristics should not be different between central laboratory and POC platforms While it is recognized that qualitative systems do provide useful information, it is recommended that POC systems provide quantitative results NACB LMPG, POC, 2007

91 Summary CLSI is an internationally recognized, consensus-based standards organization producing a large number of documents and related materials Standards and Guidelines are essential in establishing uniform good laboratory practices Standardization and traceability of methods allow commutability of results and improve quality and clinical care Although work has been done in areas of lipid and cardiac marker standardization/harmonization, further work is needed 91

92 Contact Information Speaker Barbara M. Goldsmith, Ph.D., FACB Phone: Ext 112 Address: 940 West Valley Road Suite 1400 Wayne, Pennsylvania USA 92

93 THANK YOU FOR YOUR ATTENTION 93